Potential methods for treating cancer by immunologic means are limited by incomplete understanding of the underlying physiologic mechanisms which control the production of cell mediated immunity. The experiments proposed in this project represent an attempt to develop a better scientific rationale for the selective stimulation of cell mediated immunity to some cancers. It has recently been shown that bovine serum albumin (BSA) heavily conjugated with a lipid (dodecanoic acid) selectively stimulates a type of cell-mediated immunity, delayed hypersensitivity (DTH) instead of the antibody response usually produced by stimulation with native BSA in guinea pigs. The experiments proposed in this project will include consideration of some of the physical, chemical and immunologic properties of chemically modified BSA preparations which selectively stimulate DTH. The cellular basis of the action of these antigens will be studied in vivo with special emphasis on the antigen localization and the antigen processing steps. In further experiments, we will prepare and evaluate a series of natural and synthetic materials which may serve as adjuvants to selectively enhance the production of DTH. These experiments hopefully will develop both a rationale and a protocol for stimulating strong, sustained DTH to BSA and other antigens. Parallel studies will use the information gained from these basic experiments in an attempt to stimulate DTH against purified tumor antigens and to cause regression of established tumors by immunologic methods. Selected tumor antigens will be chemically modified and injected into appropriate animals according to the protocols found most effective in selectively stimulating DTH to BSA. The cell-mediated immunity produced against the tumors in these experiments will be monitored by skin tests for DTH and by an in vitro cytotoxicity assay, and by measuring the growth and regression of tumors.